Author, as appears in the article.: Tarancon-Diez L, Rodríguez-Gallego E, Rull A, Peraire J, Viladés C, Portilla I, Jimenez-Leon MR, Alba V, Herrero P, Leal M, Ruiz-Mateos E, Vidal F, ECRIS integrated in the Spanish AIDS Research Network

Department: Medicina i Cirurgia

URV's Author/s: HERRERO GIL, POL / Peraire Forner, José Joaquin / RULL AIXA, ANNA / SIRVENT CALVERA, JUAN JOSÉ / Vidal Marsal, Francisco

Keywords: T-cells Succinate Oxidative stress Metabolomic profile Metabolism Macrophages Loss of control Immunometabolism Hiv-1 Heterogeneity Glucose Energy metabolism Elite controllers Amino-acids Absence

Abstract: Approximately 25% of elite controllers (ECs) lose their virological control by mechanisms that are only partially known. Recently, immunovirological and proteomic factors have been associated to the loss of spontaneous control. Our aim was to perform a metabolomic approach to identify the underlying mechanistic pathways and potential biomarkers associated with this loss of control.Plasma samples from EC who spontaneously lost virological control (Transient Controllers, TC, n = 8), at two and one year before the loss of control, were compared with a control group of EC who persistently maintained virological control during the same follow-up period (Persistent Controllers, PC, n = 8). The determination of metabolites and plasma lipids was performed by GC-qTOF and LC-qTOF using targeted and untargeted approaches. Metabolite levels were associated with the polyfunctionality of HIV-specific CD8+T-cell response.Our data suggest that, before the loss of control, TCs showed a specific circulating metabolomic profile characterized by aerobic glycolytic metabolism, deregulated mitochondrial function, oxidative stress and increased immunological activation. In addition, CD8+ T-cell polyfunctionality was strongly associated with metabolite levels. Finally, valine was the main differentiating factor between TCs and PCs.All these metabolomic differences should be considered not only as potential biomarkers but also as therapeutic targets in HIV infection. FUND: This work was supported by grants from Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Fondos FEDER; Red de Investigación en Sida, Gilead Fellowship program, Spanish Ministry of Education and Spanish Ministry of Economy and Competitiveness.Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.

Thematic Areas: Saúde coletiva Medicine, research & experimental Medicine (miscellaneous) Medicina iii Medicina ii Medicina i General medicine General biochemistry,genetics and molecular biology Ciências biológicas ii Biotecnología Biochemistry, genetics and molecular biology (miscellaneous) Biochemistry, genetics and molecular biology (all)

licence for use: https://creativecommons.org/licenses/by/3.0/es/

ISSN: 23523964

Author's mail: joaquim.peraire@urv.cat francesc.vidal@urv.cat

Author identifier: 0000-0001-7808-5479 0000-0002-6692-6186

Record's date: 2023-05-21

Papper version: info:eu-repo/semantics/publishedVersion

Link to the original source: https://www.sciencedirect.com/science/article/pii/S2352396419301446

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Ebiomedicine. 42 86-96

APA: Tarancon-Diez L, Rodríguez-Gallego E, Rull A, Peraire J, Viladés C, Portilla I, Jimenez-Leon MR, Alba V, Herrero P, Leal M, Ruiz-Mateos E, Vidal F, EC (2019). Immunometabolism is a key factor for the persistent spontaneous elite control of HIV-1 infection. Ebiomedicine, 42(), 86-96. DOI: 10.1016/j.ebiom.2019.03.004

Article's DOI: 10.1016/j.ebiom.2019.03.004

Entity: Universitat Rovira i Virgili

Journal publication year: 2019

Publication Type: Journal Publications